Immunization with excreted/secreted proteins in AS/n mice activating cellular and humoral response against Toxoplasma gondii infection

Costa-Silva, Thaís A.; Borges, Monamaris Marques; Galhardo, Cynthia Soares; Pereira-Chioccola, Vera Lúcia

doi:10.1016/j.actatropica.2012.08.013

Cited by 25 publications

(21 citation statements)

References 47 publications

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“…The most effective approach to vaccine development to date involves live attenuated parasites (Toxovax); however, this approach is still inadequate and cannot be used in humans due to safety concerns. Likewise, although the whole parasite lysate (TLA) or excreted/secreted parasite antigens generate protective immunity that results in high protection rates [22][23][24][25], the possibility of adverse reactions in the vaccinated individuals due to undefined antigenic composition excludes these vaccines from further research as vaccines for humans. However, these examples illustrate that multi-antigenic composition has a much greater chance of generating efficient immune responses to protect from T. gondii invasion.…”

Section: Discussionmentioning

confidence: 99%

The Impact of the Antigenic Composition of Chimeric Proteins on Their Immunoprotective Activity against Chronic Toxoplasmosis in Mice

et al. 2019

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Toxoplasmosis may pose a serious threat for individuals with weakened or undeveloped immune systems. However, to date, there is no specific immunoprophylaxis for humans. Thus, the aim of this study was to evaluate the immunogenicity of three trivalent—SAG2-GRA1-ROP1L (SGR), SAG1L-MIC1-MAG1 (SMM), and GRA1-GRA2-GRA6 (GGG)—and two tetravalent—SAG2-GRA1-ROP1-GRA2 (SGRG) and SAG1-MIC1-MAG1-GRA2 (SMMG)—chimeric T. gondii proteins, as well as their protective potential against chronic toxoplasmosis in laboratory mice. All three trivalent recombinant proteins possessed immunogenic properties, as defined by specific humoral and cellular responses in vaccinated mice characterized by the synthesis of specific IgG (IgG1/IgG2a) antibodies in vivo and the release of Th1/Th2 cytokines by stimulated splenocytes in vitro. Immunization with all three recombinant proteins provided partial protection against toxoplasmosis, although the protective capacity strongly depended on the individual antigenic composition of each preparation. The antigens providing the highest (86%) and lowest (45%) protection, SGR and SMM, respectively, were supplemented with GRA2 antigen fragment, to form the tetravalent chimeric proteins SGRG and SMMG. Further study revealed that the tetravalent preparations exhibited high immunogenic potential; however, the addition of another antigen to the recombinant protein structure had distinct effects on the protection generated, compared to that of the trivalent counterparts, depending on the antigen tested.

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Section: Discussionmentioning

confidence: 99%

The Impact of the Antigenic Composition of Chimeric Proteins on Their Immunoprotective Activity against Chronic Toxoplasmosis in Mice

et al. 2019

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“…The laboratorial diagnosis for toxoplasmosis in the 83 clinical samples was evaluated by ELISA using a tachyzoite lysate antigen (TLA) as described before [39,40]. In samples from patients with cerebral or gestational, qPCR was performed using the REP-529 molecular marker, which amplifies a highly repeatable 112 bp sequence in T. gondii genome [41].…”

Section: Laboratorial Diagnosis For Toxoplasmosismentioning

confidence: 99%

Human extracellular vesicles and correlation with two clinical forms of toxoplasmosis

et al. 2020

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“…Each 24 hours post‐infection, tachyzoites released in supernatants were recovered, separated from the ruptured cells by centrifugation (300 g , 15 minutes) and counted in Neubauer chamber. Tachyzoites were used for: (a) EV release; (b) preparing a crude tachyzoite antigen (CTA), as previously described, and used as positive control in ELISA; (c) scanning electron microscopy analyses; and (d) RNA and miRNA extraction.…”

Section: Methodsmentioning

confidence: 99%

“…The secretion by the bradyzoite cists has been proposed as a mechanism that maintains long‐lasting immunity to the parasite . However, ESA released by tachyzoites are highly immunogenic and induce protective immunity, either antibody dependent or cell mediated . CD4+ T cells specific for ESA may be involved in the maintenance of long‐term immunity in healthy chronically infected individuals, who have low anti‐ESA antibody titers.…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles isolated from Toxoplasma gondii induce host immune response

Silva

Maia

Torrecilhas

et al. 2018

Parasite Immunology

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This study established a protocol to purify Toxoplasma gondii tachyzoite microvesicles and exosomes, called as extracellular vesicles (EVs). In addition, the investigations were conducted to determine the kinetic of EV release by tachyzoites and whether EV proteins are able to modulate the host immune response. The particle size and concentration released by tachyzoites in culture medium at different incubation-period were characterized by nanoparticle tracking analysis. Tachyzoites (1 × 10 ) released around 4.37 ± 0.81 × 10 EVs/mL/h, with size varying between 138.2 and 171.9 nm. EVs released into the medium were purified by gel-exclusion chromatography and screened by ELISA, using a pool of human positive sera for toxoplasmosis. EV-fractions contained high concentration of proteins, and EVs were analyzed by scanning and transmission electron microscopies. Tachyzoites released EVs into the culture medium throughout all membrane surface, and these vesicles contain small RNAs/miRNA. Pooled sera from chronically infected human or mice (infected with 2 different T. gondii strains) recognized distinct EV electrophoretic patterns in immunoblotting. T. gondii EVs significantly induced IL-10, TNF-α and iNOS in murine macrophages. In conclusion, this study shows that T. gondii secrete/excrete EVs (microvesicles and exosomes) contain miRNA and they were immunologically recognized by host immune response.

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Immunization with excreted/secreted proteins in AS/n mice activating cellular and humoral response against Toxoplasma gondii infection

Cited by 25 publications

References 47 publications

The Impact of the Antigenic Composition of Chimeric Proteins on Their Immunoprotective Activity against Chronic Toxoplasmosis in Mice

The Impact of the Antigenic Composition of Chimeric Proteins on Their Immunoprotective Activity against Chronic Toxoplasmosis in Mice

Human extracellular vesicles and correlation with two clinical forms of toxoplasmosis

Extracellular vesicles isolated from Toxoplasma gondii induce host immune response

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